Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells.

We have recently determined that high calcium concentrations, in parallel with their suppressive effects on parathyroid hormone (PTH) secretion, reversibly and specifically decrease preproPTH mRNA in cultured bovine parathyroid cells. In order to determine whether vitamin D metabolites also regulate the content of preproPTH mRNA, we tested their effects on bovine parathyroid cells in the same culture system. Levels of preproPTH mRNA were determined by dot-blot hybridization or blot hybridization with a labeled cloned cDNA probe. Incubation with 1,25-dihydroxycholecalciferol at doses varying from 10 pM to 0.1 microM caused a direct decrease in mRNA down to 50% of control values at 48 hr. There was no evidence that 1,25-dihydroxycholecalciferol, even at the highest concentrations, had any toxic effects on cell number or viability or on total RNA or RNA synthesis. Levels of alpha-actin mRNA did not change in the same experiments, and the suppression of preproPTH mRNA was reversible. When the relative potency of various vitamin D metabolites in suppressing preproPTH mRNA was evaluated, 1,25-dihydroxycholecalciferol greater than 24,25-dihydroxycholecalciferol greater than 25-hydroxycholecalciferol greater than vitamin D3 (cholecalciferol). These effects were highly specific and suggest that vitamin D metabolites play an important role in regulating the production of PTH.